DICLOFENAC SODIUM- diclofenac sodium tablet, film coated, extended release
Denton Pharma, Inc. DBA Northwind Pharmaceuticals
Diclofenac Sodium Extended-release Tablets, USP, Tablets of 100 mg
Prescribing Information Rx only
- NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk (see WARNINGS).
- Diclofenac sodium extended-release tablets, USP are contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).
- NSAIDs cause an increased risk of serious gastrointestinal adverse events including inflammation, bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events (see WARNINGS).
Diclofenac sodium extended-release tablets, USP is a benzeneacetic acid derivative. Diclofenac sodium extended-release tablets of 100 mg (pink) are available for oral administration. The chemical name is 2-[(2,6-dichlorophenyl)amino] benzeneacetic acid, monosodium salt. The molecular weight is 318.14. Its molecular formula is C 14 H 10 Cl 2 NNaO 2 and it has the following structural formula:
The inactive ingredients in diclofenac sodium extended-release tablets include: carnauba wax, cetostearyl alcohol, colloidal silicon dioxide, compressible sugar, copovidone, gum acacia, hydroxypropyl methylcellulose, iron oxide red, magnesium stearate, polyethylene glycol, povidone, sugar, talc, titanium dioxide.
Meets USP Dissolution Test 2.
Diclofenac sodium extended-release tablets, USP are a non-steroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic, and antipyretic activities in animal models. The mechanism of action of diclofenac sodium extended-release tablets, like that of other NSAIDs, is not completely understood but may be related to prostaglandin synthetase inhibition.
Diclofenac is 100% absorbed after oral administration compared to IV administration as measured by urine recovery. However, due to first-pass metabolism, only about 50% of the absorbed dose is systemically available (see Table 1). When diclofenac sodium extended-release tablet is taken with food, there is a delay of 1 to 2 hours in the T max and a two-fold increase in C max values. The extent of absorption of diclofenac, however, is not significantly affected by food intake.
|PK Parameter|| Normal Healthy Adults
|Mean||Coefficient of Variation (%)|
|Absolute Bioavailability (%) [N = 7]||55||40|
|T max (hr) [N = 12]||5.3||28|
|Oral Clearance (CL/F; mL/min) [N = 12]||895||56|
|Renal Clearance (% unchanged drug in urine) [N = 7]||<1|| —
|Apparent Volume of Distribution (V/F; L/kg) [N = 56]||1.4||58|
|Terminal Half-life (hr) [N = 56]||2.3||48|
The apparent volume of distribution (V/F) of diclofenac sodium is 1.4 L/kg. Diclofenac is more than 99% bound to human serum proteins, primarily to albumin. Serum protein binding is constant over the concentration range (0.15 — 105 μg/mL) achieved with recommended doses.
Diclofenac diffuses into and out of the synovial fluid. Diffusion into the joint occurs when plasma levels are higher than those in the synovial fluid, after which the process reverses and synovial fluid levels are higher than plasma levels. It is not known whether diffusion into the joint plays a role in the effectiveness of diclofenac.
Five diclofenac metabolites have been identified in human plasma and urine. The metabolites include 4’-hydroxy-, 5-hydroxy-, 3’-hydroxy-, 4’, 5-dihydroxy- and 3’-hydroxy-4’-methoxy diclofenac. The major diclofenac metabolite, 4′-hydroxy-diclofenac, has very weak pharmacologic activity. The formation of 4′-hydroxy diclofenac is primarily mediated by CPY2C9. Both diclofenac and its oxidative metabolites undergo glucuronidation or sulfation followed by biliary excretion. Acylglucuronidation mediated by UGT2B7 and oxidation mediated by CPY2C8 may also play a role in diclofenac metabolism. CYP3A4 is responsible for the formation of minor metabolites, 5-hydroxy- and 3’-hydroxy-diclofenac. In patients with renal dysfunction, peak concentrations of metabolites 4’-hydroxy- and 5-hydroxy-diclofenac were approximately 50% and 4% of the parent compound after single oral dosing compared to 27% and 1% in normal healthy subjects.
Diclofenac is eliminated through metabolism and subsequent urinary and biliary excretion of the glucuronide and the sulfate conjugates of the metabolites. Little or no free unchanged diclofenac is excreted in the urine. Approximately 65% of the dose is excreted in the urine and approximately 35% in the bile as conjugates of unchanged diclofenac plus metabolites. Because renal elimination is not a significant pathway of elimination for unchanged diclofenac, dosing adjustment in patients with mild to moderate renal dysfunction is not necessary. The terminal half-life of unchanged diclofenac is approximately 2 hours.
When co-administered with voriconazole (inhibitor of CYP2C9, 2C19 and 3A4 enzyme), the Cmax and AUC of diclofenac increased by 114% and 78%, respectively (see PRECAUTIONS, Drug Interactions).
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